Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium butyrate has been shown to inhibit the growth and induce the differentiation of F-98 rat glioma cells. In agreement with the morphological changes, we have found that mRNAs for fibronectin and collagen in these cells could be reversibly induced by butyrate. While Ki-ras mRNA levels remained relatively unchanged, mRNAs for fos and sis increased significantly during the course of butyrate induced differentiation. c-fos induction can be detected 30 min after butyrate addition, a peak level (greater than 20 fold) was reached at 2 h, with a subsequent gradual decline. c-sis induction was detectable 24 h after butyrate exposure, at which time the cells have assumed morphological transition. Interestingly, the sis mRNA induction was not reversible upon butyrate withdrawal. The sis mRNA half-life increased from 40 min in the untreated cells to 100 min in the butyrate induced cells indicating that the increase in the stability of sis mRNA contributed, at least in part, to the elevated levels of sis expression. These findings demonstrate a coordinated induction of fibronectin and collagen genes in the butyrate-treated F-98 cells. In addition, fos and sis transcripts were differentially induced; a rapid and transient induction of fos followed by an irreversible induction of sis at a later stage of differentiation.
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PMID:Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. 210 2

Sodium butyrate (NaB), when added to cell cultures, produces a variety of morphological and biochemical changes. We examined its effects, in nM concentrations, on the expression of two glioma cell-associated proteins, glial fibrillary acidic protein (GFAP) and S-100 protein in human glioma-derived cell line (RF), and of S-100 protein in the C6 rat glioma cell line. GFAP levels decreased by about 50% in the RF cell line, and S-100 protein levels decreased protein levels decreased by about 40% after treatment with 1 mM NaB for 48 h. In the C6 rat glioma cell line, isoproterenol with theophylline was found to increase S-100 levels by two-fold over basal levels. NaB was found to inhibit the induction of S-100 protein but exhibited no effect on the basal levels of the protein. Other short chain fatty acids, including sodium propionate and sodium isobutyrate, exhibited partial inhibitory activity. NaB, at an EC50 of 1 mM, was also found to inhibit both the beta-adrenergic and the forskolin-mediated increase in cAMP levels in these cells. This suggests that NaB may inhibit cells from expressing S-100 protein by attenuating cAMP levels.
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PMID:Effect of sodium butyrate on S-100 protein levels and the cAMP response. 282 31

Cellular differentiation of the neuroblastoma X glioma hybrid cell line NG108-15 was measured and correlated with quantitative changes in the cells' ganglioside composition. The degree of differentiation was measured using an enzymatic marker, choline acetyltransferase (CAT), which is responsible for neurotransmitter synthesis in this cell line. Differentiation of these cells is commonly induced by agents such as dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). However, in our studies, we observed that these cells "self-differentiated," in the absence of chemical inducers, when the cells became dense in culture. The differentiation marker, CAT specific activity, rose from 150 to more than 400 pmol/min/mg of protein as cell density increased, attaining a level higher than that achieved by treatment with Bt2cAMP. Differentiation of sparse cultures could be induced by conditioned medium removed from dense cultures. This effect was not due to depletion of a serum component from the medium by the cells, since it was not mimicked by serum depletion or inhibited by addition of fresh serum to the conditioned medium. These data suggest that cell density-dependent differentiation was caused by release of a factor from the cells which induced differentiation in a concentration-dependent manner. Gangliosides, therefore, were purified from sparse control cultures, dense cultures, and cultures treated with the differentiating agents Bt2cAMP, prostaglandin E1 (plus theophylline), or butyric acid. Quantitative thin layer chromatography revealed that all of the cultures contained the four gangliosides GM3, GM2, GM1, and GD1a. The concentration of one of the gangliosides, GM2, increased markedly (up to 12-fold) during differentiation. The GM2 concentration correlated closely with the level of CAT activity in the different cultures (r = 0.99). These data demonstrate that the ganglioside concentration in these cells is regulated during differentiation, a finding consistent with a possible role for gangliosides in the differentiated phenotype.
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PMID:Ganglioside composition is regulated during differentiation in the neuroblastoma X glioma hybrid cell line NG108-15. 630 Mar 57

1. Alniditan, a novel migraine abortive agent, is a potent 5-HT1B/5-HT1D receptor agonist of nM affinity. We compared the agonistic properties of alniditan, sumatriptan and dihydroergotamine on the cloned human 5-HT1B receptor expressed at 200 fmol mg(-1) protein (Bmax) in non-induced L929sA cells, at 740 fmol mg(-1) protein in HEK 293 and at 2300 fmol mg(-1) protein in mIFNbeta-induced L929sA cells, and on the human cloned 5-HT1D receptor expressed in C6 glioma cells (Bmax 780 fmol mg(-1) protein). 2. Sodium butyrate treatment increased the expression level of human (h)5-HT1B receptors in HEK 293 cells and h5-HT1D receptors in C6 glioma cells approximately 3 fold, the binding affinities of [3H]-5-HT and [3H]-alniditan were unaffected. 3. Agonistic properties were evaluated based on inhibition of cyclic AMP accumulation in the cells after stimulation of adenylyl cyclase by forskolin or isoproterenol. Alniditan, sumatriptan and dihydroergotamine were full agonists at the hS-HT1B receptor (IC50 values were 1.7, 20 and 2 nM, respectively in HEK 293 cells) and hS-HT1D receptors (IC50 values of 1.3, 2.6 and 2.2 nM, respectively). At the h5-HT1B receptor the agonist potency of the compounds slightly increased with higher receptor density. The opposite was seen for antagonists (ocaperidone, risperidone and ritanserin). 4. This comparative study demonstrated that alniditan was 10 times more potent than sumatriptan at the h5-HT1B receptor, and twice as potent at the h5-HT1D receptor. Dihydroergotamine was more potent an agonist at the h5-HT1B receptor when expressed at high and low level in L929sA cells (but not in HEK 293 cells), and was less potent at the hS-HT1D receptor.
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PMID:Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. 960 73

Previously we reported that the co-culture of non-brain vascular endothelial cells with glioma cells leads to the induction of a more differentiated endothelial cell phenotype which exhibits important properties of the blood-brain barrier (BBB). Recognising the potential for improving the model barrier system with agents known to modify the growth and differentiation of cells in culture we examined the effects of four differentiating agents (butyric acid, dexamethasone, retinoic acid, and dimethyl sulfoxide) on barrier function. Of these agents only butyric acid and dexamethasone resulted in an enhancement (depending on the dose used) of transendothelial electrical resistance (barrier function). The greatest effect was observed with butyric acid in a dose-dependent manner and was slow in onset and only occurred in the endothelial/glial cell co-cultures. These data indicate that butyric acid may be a beneficial agent in optimising conditions necessary for induction of BBB properties in in vitro barrier systems.
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PMID:Butyric acid mediated induction of enhanced transendothelial resistance in an in vitro model blood-brain barrier system. 1045 56

We developed an adenovirus vector for transduction of the human CD21 gene (Adv-CD21), the Epstein-Barr virus (EBV)-specific receptor on human B lymphocytes, to overcome the initial barrier of EBV infection in nonprimate mammalian cells. Inoculation of Adv-CD21 followed by exposure to recombinant EBV carrying a selectable marker resulted in the successful entry of EBV into three of seven nonprimate mammalian cell lines as evidenced by expression of EBV-determined nuclear antigen (EBNA). The EBV-susceptible cell lines included rat glioma-derived 9L, rat mammary carcinoma-derived c-SST-2, and canine kidney-derived MDCK. Subsequent selection culture with G418 yielded drug-resistant cell clones. In these cell clones, EBV existed as an episomal form, as evidenced through the Gardella gel technique. Among the known EBV latency-associated gene products, EBV-encoded small RNAs, EBNA1 and transcripts from the BamHI-A rightward reading frame (BARF0), and latent membrane protein 2A were expressed in all EBV-infected cell clones. The viral lytic events could be induced in these cell clones by simultaneous treatment with 12-O-tetradecanoylphorbol-13-acetate and n-butyric acid, but they were abortive, and infectious virus was not produced. These results indicate that once the initial barrier for attachment is overcome artificially, EBV can establish a stable infection in some nonprimate mammalian cells, and they raise the possibility that transgenic animals with the human CD21 gene could provide an animal model for EBV infection.
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PMID:CD21-mediated entry and stable infection by Epstein-Barr virus in canine and rat cells. 1104 19

Sodium butyrate is well known in stimulating growth and differentiation of cancer cells. In the present study, butyrate treatment caused decreases in thymidine incorporation in the early passages (45-60) of C6 glioma cells. In addition, butyrate also caused decreases in inositol incorporation and transient ATP-stimulated Ca2+ mobilization suggesting that butyrate altered general mechanisms of Ca2+ signaling in these cells. To gain direct insight into the crosstalk between sodium butyrate and Ca2+ signaling in transcriptional regulation, we investigated the induction of the Ca2+-sensitive immediate early genes (IEGs), c-fos, nur77 and c-myc. Sodium butyrate per se enhanced the expression of c-fos mRNA, and the enhanced levels were maintained for 24 h, but over the same time period, the initially increased levels of nur77 expression tailed off, while c-myc expression was slightly reduced. Increasing intracellular Ca2+ concentration ([Ca2+]i) by thapsgargin and A23187 induced the expression of both c-fos and nur77 mRNA expression, and synergistic effects were observed when cells were incubated with sodium butyrate plus thapsgargin and A23187. However, removal of both extracellular Ca2+ by EGTA, or intracellular free Ca2+ with BAPTA did not affect the sodium butyrate-induced c-fos and nur77 mRNA. These results suggest that although sodium butyrate altered Ca2+ signaling which is an important regulatory mechanism for c-fos and nur77 expression, nevertheless the sodium butyrate-induced c-fos and nur77 expression may be not in fact mediated through Ca2+ signaling.
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PMID:Alterations in Ca2+ signaling, and c-fos and nur77 expression are associated with sodium butyrate-induced differentiation of C6 glioma cell. 1129 79

Inducible nitric oxide synthase (iNOS) plays a significant role in the pathology of central nervous system diseases. Inducible NOS expression is regulated by intracellular adenosine 3',5'-cyclic monophosphate (cAMP) signaling, and astrocytes contain both iNOS and adenylate cyclase-coupled neurotransmitter receptors. The data obtained from the present study indicated that acetylcholine, lambda-amino-n-butyric acid, glutamate, quinolinic acid, N-methyl-D-aspartate and aspartate have no effect on NO(2)(-) production in C6 glioma cells stimulated by lipopolysaccharide and interferon-gamma. However, dopamine (DA) caused inhibition of NO(2)(-) production and iNOS transcription. The effects of DA were not due to homovanillic acid/3,4-dihydroxyphenylacetic acid, the autoxidative products superoxide (O(2)(-))/hydrogen peroxide (H(2)O(2)) or direct reactions with NO(2)(-). Forskolin, adenylate cyclase activator, dose-dependently reduced NO(2)(-). Meanwhile, (+/-) SKF-38393 D(1) receptor agonist attenuated iNOS in a similar fashion to DA. In addition, the results indicated that DA attenuation of iNOS was significantly impeded by the adenylate cyclase inhibitor MDL-12,330A, the D(1) antagonist SCH-23390, the beta2 adrenergic receptor antagonist ICI-118,551 and the beta1 adrenergic receptor antagonist atenolol. In conclusion, it appears that DA attenuates iNOS through a D(1), beta1 and beta2 adrenergic receptor-linked adenylate cyclase-mediated cAMP cascade.
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PMID:Characterization of neurotransmitters and dopamine attenuation of inducible nitric oxide synthase in glioma cells. 1245 38

Histone deacetylase (HDAC) inhibitors have both apoptotic and differentiating effects on various tumor cells. However, the mechanisms underlying the effect of HDAC inhibitors remain unclear. In this study, we investigated the function of anti-proliferative effects of HDAC inhibitors, N-butyric acid and trichostatin A, on human malignant glioma cell lines, U251-MG and D54. MTT assay showed a dose-dependent inhibition of cellular proliferation in both cell lines. Cell cycle analysis revealed increased sub-G1 population in both lines, and G1 arrest only in U251-MG cells. Induction of apoptosis was also supported by the occurrence of DNA fragmentation in tumor cells treated with HDAC inhibitors. Furthermore, caspase inhibition assay indicated that HDAC inhibitor-induced apoptosis was caspase-dependent. Neither mitochondrial membrane potential nor the expression of caspase-9 was changed by treatment with HDAC inhibitors, suggesting the possibility that HDAC inhibitor-induced apoptosis was not mediated by the mitochondrial cell death pathway. On the other hand, immunoblot assay confirmed increased expression of caspase-8 in both lines, and elevation of p21 but not p27 protein in U251-MG cells following HDAC inhibitor treatment. Taken together, the HDAC inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis with or without p21-mediated G1 arrest in human malignant glioma cells.
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PMID:Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells. 1580 27

Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate (AN-1), induced hyperacetylation, increased p21(Cip1) expression, inhibited proliferation, and enhanced apoptosis. Histone deacetylase inhibitor-induced apoptosis was mediated primarily by caspase-8. Treatment of cells with AN-1 or AN-9 for 24 hours before exposure to gamma-irradiation potentiated further caspase-8 activity and resultant apoptosis. Clonogenic survival curves revealed marked reductions in cell renewal capacity of U251 MG cells exposed to combinations of AN-1 and radiation. Preliminary in vivo experiments using human glioma cell lines grown as xenografts in mouse flanks suggest in vivo efficacy of AN-9. The data suggest that novel butyric acid prodrugs provide a promising treatment strategy for malignant gliomas as single agents and in combination with radiation therapy.
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PMID:Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas. 1637 10


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